study to evaluate apvo210 in healthy subjects, patients with psoriasis, and patients with ulcerative colitis

Conditions: Psoriasis; Ulcerative Colitis

Summary: phase 1 study in 2 stages with 2 expansion cohorts. the first stage is a single ascending dose (sad) study of apvo210 in healthy volunteers. the second stage is a multiple ascending dose (mad) study of apvo210 in healthy volunteers. two expansion cohorts evaluate multiple doses of apvo210 in psoriasis patients and ulcerative colitis patients.


Eligibility criteria:
inclusion criteria: main inclusion criteria: * age 18 to 65 years old. * body mass index (bmi) \> 18.5 kg/m2 and \< 30.0 kg/m2; minimum body weight of 50 kg. * good health and no clinically significant findings on: * physical examination * 12-lead ecg * clinical laboratory tests (serum chemistry, haematology, coagulation, urine drug screen, and urinalysis (ua)) * seated systolic blood pressure (bp) 90 to 140 mm hg. * seated diastolic bp 60 to 90 mm hg. psoriasis patients (expansion cohort): main inclusion criteria: * clinical diagnosis of chronic plaque psoriasis with a disease duration of at least 6 months; patients with concurrent psoriatic arthritis may be enrolled. * psoriasis area and severity index (pasi) score ≥ 12 at baseline. * psoriasis plaque bsa (body surface area) ≥ 10% * pga (physician global assessment) ≥ 3. * age 18 to 65 years old. * body mass index \> 18.5 and \< 35.0 kg/m2; minimum body weight of 50 kg. ulcerative colitis patients (expansion cohort): main inclusion criteria: * moderately to severely active ulcerative colitis as defined by: * baseline mayo score of 6 to 12; and * endoscopic sub-score ≥2 as read by central reader * is intolerant, refractory, or only partially responsive to corticosteroids (not including budesonide), immunomodulators (azathioprine \[aza\] or 6-mercaptopurine \[6-mp\], and methotrexate), or biologics. * age 18 to 65 years old. * body mass index \> 18.5 and \< 35.0 kg/m2; minimum body weight of 50 kg. exclusion criteria: main exclusion criteria * clinically significant manifestation of metabolic; hepatic; renal; haematological; pulmonary; cardiovascular; gastrointestinal; musculoskeletal; dermatological; urogenital; eye, ear, nose, and throat; psychiatric; or neurological disorders. * alanine aminotransferase (alt) or aspartate aminotransferase (ast) \> 1.2 times the upper limit of normal (uln) as defined by the laboratory. * positive hepatitis panel (hepatitis b surface antigen \[hbsag\] and anti-hepatitis c virus \[hcv\]) or positive human immunodeficiency virus (hiv) antibody. * positive quantiferon tuberculosis (tb) test at screening visit. * receipt of live vaccine less than 1 month prior to check in or plan to receive live vaccine during the study or up to 3 months following end of treatment visit. * infection in the 4 weeks prior to check-in that required hospitalization or parenteral antibiotics. psoriasis patients (expansion cohort): main exclusion criteria: * history of malignancy, diagnosed or known to be active or actively treated within the past 5 years, other than resected lesions of low malignant potential, such as basal cell skin cancers or low risk squamous cell carcinomas of the skin. * alanine aminotransferase (alt) or aspartate aminotransferase (ast) \> 2 times the upper limit of normal (uln) as defined by the laboratory. * creatinine \> 1.5 times uln as defined by the laboratory. * positive hepatitis panel (hepatitis b surface antigen \[hbsag\] and anti-hepatitis c virus \[hcv\]) or positive human immunodeficiency virus (hiv) antibody. * positive quantiferon tuberculosis (tb) test at screening visit. * receipt of live vaccine less than 1 month prior to check in or plan to receive live vaccine during the study or up to 3 months following end of treatment visit. * infection in the 4 weeks prior to check-in that required hospitalization or parenteral antibiotics. * use of a prescription medication that could have an effect on psoriasis (eg, lithium, systemic steroids, immunosuppressants) during the 14 days before check-in; use of prescription medications for psoriasis is not permitted until after the follow-up visit. * non plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular). * use of biologic agents (eg, adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab, guselkumab, tildrakizumab, brodalumab) or psoralen and ultraviolet a (puva) within 12 weeks prior to check-in, ultraviolet b (uvb) phototherapy, use of tanning beds, or use of systemic medications such as methotrexate, cyclosporine a, acitretin, tofacitinib or apremilast within 4 weeks prior to check-in, or topical anti-psoriasis medications (except emollients) within 2 weeks prior to check-in. ulcerative colitis patients (expansion cohort): main exclusion criteria: * ulcerative colitis requiring immediate surgical, endoscopic, or radiological intervention including massive haemorrhage, perforation and sepsis, suppurative complications, or toxic colon. * stool positive for clostridium difficile toxin, enteric pathogens, or ova and parasites. * positive hepatitis panel (hepatitis b surface antigen \[hbsag\] and anti hepatitis c virus \[hcv\]) or positive human immunodeficiency virus (hiv) antibody. * positive quantiferon tuberculosis (tb) test at screening visit. * receipt of live vaccine less than 1 month prior to check in or plan to receive live vaccine during the study or up to 3 months following end of treatment visit. * infection in the 4 weeks prior to check-in that required hospitalization or parenteral antibiotics. * use of biologic agents (eg, adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab, guselkumab, tildrakizumab, brodalumab) or psoralen and ultraviolet a (puva) within 12 weeks prior to check-in, ultraviolet b (uvb) phototherapy, use of tanning beds, or use of systemic medications such as methotrexate, cyclosporine a, acitretin, tofacitinib or apremilast within 4 weeks prior to check-in, or topical anti-psoriasis medications (except emollients) within 2 weeks prior to check-in.